Traumatic brain injury (TBI) is a serious public health problem resulting in death or permanent disability. In fact, according to the Centers for Disease Control and Prevention, in the U.S. alone, about two million TBIs occur every year either as an isolated injury or along with other injuries. Further, TBI is a contributing factor to about one third of all injury-related deaths in the U.S. TBI can cause neurological disorders such as neurodegeneration, memory deficits, and sleep disorders, as well as non-neurological disorders such as systemic metabolic dysregulation.
Yet, despite the urgent need for effective therapeutics for the treatment of TBI, none have been developed to date. Drug candidates tested in established animal models (predominantly rats and mice) have all failed in clinical trials. The failure to develop therapies is likely due to the complexity of TBI, both in terms of the severity and spatial distribution of injury to the brain and the elaborate responses of the brain to injury. In addition, a major disadvantage of established TBI models is that they are not amenable to large phenotypic screens, e.g., small molecule library screens, RNAi screens, or mutagenesis screens. Thus, there is an ongoing need for model systems of TBI that allow for medium to high-throughput identification of TBI-relevant genetic pathways and candidate therapeutic agents.